Fibrogenesis, which produces extracellular matrixes including collagen as a typical example, is a mechanism of wound healing. However, if injury is prolonged, it deviates from a usual process, and the extracellular matrix is excessively deposited over a wide range, resulting in the development of fibrosis. Fibrosis is observed in various organs, but the origins of extracellular matrix-producing cells are considered to be the same. Such origins are considered to be endogenous fibroblasts, epithelial cells that have undergone epithelial-mesenchymal transition, and fibrocytes (Non Patent Document 1). Fibrosis is a disease in which functional disorder occurs as a result of the damage of a tissue itself due to a causal disease and the subsequent fiber forming, resulting in organ failure. This disease has poor prognosis.
To date, suppression of inflammatory response has been attempted to treat fibrosis, but sufficient effects could not be obtained from such treatment. Studies have been conducted to develop an antifibrotic agent that targets fibrosis regulatory factors, such as TGF (Transforming Growth Factor)-β1, VEGF (Vascular Endothelial Growth Factor), PDGF (Platelet-Derived Growth Factor) and angiotensin H (Non Patent Document 2).
Pirfenidone has been applied as only such an antifibrotic agent to idiopathic pulmonary fibrosis. The effectiveness of pirfenidone recognized in clinical tests has been only suppression of a decrease in vital capacity. In addition, pirfenidone has had side effects such as photosensitivity in 87.9% of subjects (Non Patent Document 3). Hence, application of pirfenidone is not a sufficient therapeutic method in terms of both effectiveness and safety.
A main ingredient of an extracellular matrix that is excessively deposited in fibrosis is collagen. Among others, the most abundant collagen is type I collagen. Accordingly, a substance that inhibits production of collagen is useful for the prevention or treatment of diseases attended with fibrosis lesion.
To date, it has been reported that an anthranilic acid derivative has action to inhibit production of matrix metalloprotease-13 (Patent Document 1). However, it has been completely unknown that the anthralinic acid derivative has action to suppress production of collagen.